In the present study, we evaluated the relationship between the GNRI score and the long-term outcomes of HCC after hepatectomy. In the entire cohort, the clinicopathological characteristics were different between the two groups; therefore, PSM was applied to overcome that bias. After PSM, the high-GNRI group demonstrated significantly better RFS and OS according to the log-rank test, and a high GNRI was an independent prognostic factor of better RFS and OS in multivariate analyses. Thus far, only one study has mentioned the relationship between GNRI and the prognosis of HCC. Li et al. reported that a low GNRI resulted in a worse prognosis in HCC; however, their study was limited to hepatitis B virus-associated HCC and patients aged 65 years or older16. To the best of our knowledge, this is the first study that evaluated the relationship between GNRI and the long-term outcomes of HCC to include patients younger than 65 years and whole underlying liver disease in HCC.
Many studies have described the usefulness of sarcopenia with respect to postoperative complications and cancer prognosis18, 19. Although sarcopenia is a powerful tool to evaluate nutritional status, the measurements are complex. Measurements of calf circumference, 6-meter walking time, handgrip strength, 5-times sit-to-standing time, and/or the area of the iliopsoas muscle at the third lumbar vertebra level on CT, etc., are required. On the other hand, the GNRI is an objective, inexpensive, and readily available assessment tool of nutritional status. Only serum albumin level, body height, and weight are needed to calculate the GNRI. Shoji et al. reported a correlation between the area of the iliopsoas muscle at the third lumbar vertebra level and the GNRI score20. Besides, Cereda and Vanotti indicated that the GNRI was associated with mid-upper arm muscle circumference, arm muscle area, handgrip strength, and handgrip strength/arm muscle area21. Therefore, the GNRI may be a useful tool for predicting postoperative complications and prognosis, especially in patients in whom evaluating sarcopenia is challenging and in institutes that lack the appropriate measuring equipment.
Serum albumin concentration is the main screening tool for immune nutritional status. Hypoalbuminemia induces an impaired immune response, and immunity has a strong influence on cancer prognosis22, 23. Additionally, a low albumin level is associated with elevated inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1, and interleukin-6, which may lead to the progression of HCC24, 25. Therefore, a low GNRI may reflect impaired tumor immunity which may cause cancer progression.
BMI is also an immune nutritional index, and several recent studies have mentioned an association between BMI and the response to immune checkpoint inhibitors26, 27. A high BMI was reported to be associated with improved survival in patients treated with immune checkpoint inhibitors. Cortellini et al. reported that adipose tissue could activate cytotoxic T-cells and decrease regulatory T-cells. Thus, BMI might influence host immunity. The GNRI is based on serum albumin concentration and BMI, and high values for these components can positively influence host immunity which may improve the cancer prognosis.
Our results indicated that preoperative malnutrition causes worse outcomes after hepatectomy in HCC. Interventions aimed at preoperative nutritional status will improve not only short-term outcomes but also cancer prognosis. Several studies have demonstrated that perioperative nutritional support improves morbidity and prognosis28–30. Therefore, we believe that perioperative immune nutritional support should be performed intensively for patients who are planned to undergo hepatectomy.
The present study has some study limitations. First, there is a potential risk of selection bias owing to the single-center, retrospective design. Prospective, multi-institutional studies are needed to validate our results. Second, postoperative complications were not assessed in the present study.
In conclusion, the GNRI is an objective, inexpensive, and easily calculated assessment tool for nutritional status. Our findings suggest that GNRI can be a useful predictor of survival in HCC after hepatectomy. Perioperative nutritional support might improve cancer survival.